Epithelial cells lining exposed mucosal surfaces, such as the gastrointestinal, respiratory and genito-urinary tracts, express the polymeric immunoglobulin receptor (pIgR). The pIgR binds to IgA at the basolateral surface of the epithelial cell. The pIgR-IgA complex is endocytosed, transcytosed and the IgA is released at the apical surface of the cell. The IgA discharged into secretions forms the first immunological defense against mucosal infections, which account for greater than 95% of human infectious diseases. Mucosal infections include many high priority diseases such as AIDS, as well as emerging and re-emerging diseases, such as TB and multiple antibiotic resistant bacteria. Moreover, it was recently discovered that as the IgA is being transcytosed across the cell, it can neutralize viruses within the cell, and that this is a major mechanism of antiviral immunity. The most effective strategy for control of mucosal infections is mucosal vaccination. The goal of this research is to understand the molecular mechanism of transcytosis of IgA. This is crucial to understanding the mucosal immune response and the development of mucosal vaccines. The transcytotic pathway of the pIgR across the cell and the possible points where it can intersect with and neutralized intracellular virus will be determined. Syntaxins, ARF, and coat proteins are families of proteins that are known to be involved in protein traffic in non-polarized cells. Their roles in the movement of the pIgR across polarized epithelial cells will be analyzed. Other proteins that interact with these proteins or with the pIgR will also be identified and their roles examined.